Although there are many different herbs used for
medicinal purposes, this discussion will be limited to several herbs that are
most often encountered and used by the general population (Table
1). Additional information can be found on the
Internet as well as in the Physician's Desk Reference for Herbal Medicine.5 Echinacea (Echinacea purpurea) - The "Purple Cone-flower" is
native to North America. It was used by the Plains Indians for its medicinal
properties and the Indians introduced it to European settlers. Currently, it is
usually marketed alone or in combination with other herbs as a purported "immune
booster", especially for the prevention or treatment of colds. In 1998, a
double-blind, randomized study of 302 military volunteers given echinacea for
prevention of upper respiratory infections (URI) speculated that there may be a
10-20% risk reduction for contracting an URI, even though a definitive
prophylactic effect could not be demonstrated.6
The plant contains water-soluble polysaccharides that strongly affect the
immune system. Effects include stimulating phagocytosis, increasing motility of
leukocytes, and increasing the production of T lymphocytes and interferon.7
Similarly, animal studies show that components of echinacea increase the number
of circulating white blood cells, enhance phagocytosis, stimulate cytokine
production, and trigger the alternative complement pathway.8
Although echinacea is generally thought to be "safe", it does have the
potential for side effects such as allergic reactions, especially in atopic
patients, nausea and vomiting, and hepatotoxicity if used with other potentially
hepatotoxic drugs.36 Other possible problems
with echinacea include suppression of the immune system if used chronically. Ephedra (ma huang) (Ephedra sinensis) - Native to central
Asia, Ephedra has been used in traditional Chinese medicine for more than 5,000
years. It is used primarily as a remedy for bronchial asthma, but is also used
to treat symptoms of cold and flu, including fever, chills, cough, wheezing,
headache, and nasal congestion. The plant contains the alkaloids ephedrine and
pseudoephedrine, which are central nervous system stimulants. They enhance the
release of norepinephrine and stimulate both alpha and beta-adrenergic
receptors. Desired effects induce bronchodilation, decreased bronchial edema,
and vasoconstriction. Ephedra is also used as a stimulant and appetite
suppressant. The weight loss mechanisms of action include an anorectic effect
via adrenergic pathways in the hypothalamus and a thermogenic effect due to
increased metabolic rate.
Side effects that may be associated with the use of Ephedra include
insomnia, nervousness, irritability, dry mouth, headache, generalized weakness
and dizziness. Hypertension, palpitations, tachycardia, stroke and seizures are
all signs of severe cardiovascular instability that been reported following
Ephedra use. Feverfew(Tanacetum parthenium) - This daisy-like perennial
commonly found in gardens and along roadsides is used for moderation and
prevention of migraine headaches. It has been used since ancient times for its
pain-relieving properties as well as an antipyretic. The first century Greek
physician Dioscorides prescribed feverfew for "all hot inflammations."8
It has been used as a folk medicine for menstrual cramps since Greco-Roman
times. In modern times, Canadian health officials recently approved encapsulated
feverfew leaves as an over-the-counter medication for migraine prophylaxis. This
indication was based on a double-blind, placebo controlled trial of 270 patients
in which feverfew use was associated with a 70% reduction in migraine frequency
and severity.9 Other studies did not show the
same rate of migraine prevention, possibly because a different source of the
herb was used. This discrepancy points out the difficulties in herbal studies,
due to the variability of the contents and effects of different preparations of
the same herb, as well as the inability to standardize the samples to identical
ingredients. Laboratory evidence indicates that feverfew causes vasodilatation
and reduces inflammation. Active ingredients inhibit phagocytosis, platelet
aggregation, and secretion of inflammatory mediators such as arachidonic acid
and serotonin.10 Feverfew is thought to
down-regulate the cerebrovascular response to endogenous amines, consistent with
its ability to prevent but not abort headaches. Side effects include up to a 15%
incidence of users developing aphthous ulcers and/or gastrointestinal tract
irritation. Rebound headaches may occur with the sudden discontinuation of the
herb. Garlic (Allium sativum) - Garlic is one of the world's
most-used herbs, both now and throughout history. Louis Pasteur first
demonstrated its antiseptic activity. Its uses now include therapy for
atherosclerosis, antibacterial, antiviral, antifungal, and even as an anticancer
agent. The main purported active ingredient is allicin, which is thought to be
effective in blood lipid reduction (mainly low-density lipoprotein). Allicin is
also reported to decrease platelet aggregation and increase fibrinolytic
activity, clotting time, and streptokinase-induced plasminogen activation. The
activity of the herb is destroyed by heat and acid; thus, raw garlic cloves, or
enteric-coated tablets need to be consumed to optimize its effects. Side effects
include malodorous body odor, allergies to the enteric coating, contact
irritation, heartburn, and flatulence. As with many herbal products, the quality
of commercial preparations varies greatly, and many products contain far less of
the active ingredient than is indicated on the label. Ginger (Zingiber officinale) - Ginger has been a popular
culinary and medicinal herb for thousands of years. The Chinese, as well as
numerous other cultures and civilizations, have used it in ancient times as a
digestive aid and antiemetic. References to it have been recorded in early
Chinese and Sanskrit texts, and in ancient Greek, Roman, and Arabic medical
literature. The ginger root contains oleoresin (composed of gingerols and
shogaols), as well as non-pungent substances and volatile oils. The exact
mechanism of antiemetic action is not known for certain, but several of the
active components are known to antagonize serotonin type 3 receptors. Extracts
of the root have also been shown to inhibit thromboxane synthetase and reduce
thromboxane B2 formation and platelet prostaglandin endoperoxides.11
Although ginger is commonly used for nausea and vomiting, if taken in large
quantities, it may cause heartburn or stomach distress. Tachycardia and
hypertension are also side effects that may be associated with the use of
ginger. Ginkgo (Ginkgo biloba) - The ginkgo tree is the world's
oldest living tree species. Its seeds and fruits have been used as medicine in
China since 2800 B.C.E. It has become an increasingly popular herbal remedy for
improvement of circulation, memory and mental function, as well as a possible
treatment and prevention for Alzheimer's disease. A recent review showed
positive results in treatment of Alzheimer's disease with ginkgo.12
Other reports have reported a slight decrease in the rate of decline in patients
with mild to moderately severe dementia due to Alzheimer's disease.13
Extracts of the leaves are used as a dietary supplement. The
extract contains three types of flavonol glycosides, which are believed to have
antioxidant activity. Terpene lactones also found in the extract improve the
circulation by a dilatory effect on the blood vessels. Hence the use of ginkgo
to treat circulatory disorders such as varicosities, postthrombotic syndrome,
chronic cerebral vascular insufficiency, tinnitus, vertigo, claudication, and
Raynaud's disease. Both types of active constituents appear to inhibit platelet
aggregation. Side effects may include headache, gastrointestinal disturbances,
and allergic skin reactions. Increased bleeding may occur, especially in
patients taking ginkgo along with other anticoagulants such as coumadin,
heparin, aspirin, or even NSAID's. Other drug interactions may include
hypertension when ginkgo is used along with thiazide diuretics. Ginseng (Panax ginseng) Panax quinquefolius - American
ginseng - endangered species, Eleutherococcus senticosus - Siberian
ginseng - Not in the Panax (true ginseng) genus, but has similar chemical
actions. However, several other products labeled as ginseng do not contain the
active ingredients ginsenosides. Consumers should beware of anything labeled
"American Red Ginseng", "wild American Ginseng," or "wild Red Desert Ginseng",
as these herbs are not botanically, chemically, or pharmacologically related to
the true ginseng root.
Ginseng is one of the most popular and expensive herbs in the world. In
ancient China it was considered to be a panacea, and the common name of ginseng
("man-root") stems from a belief that, because this root is humanoid in
appearance, it can benefit all aspects of the human body. Its genus name of
Panax means "cure-all". More than six million Americans use this root for
medicinal purposes. Retail sales in 1998 were more than $95 million. Most of the
uses of this root are as a tonic or adaptogen that enhances physical performance
(including sexual), promotes vitality, and increases resistance to stress and
aging. It has antioxidant properties as well as appears to have a modulating
effect on the hypothalamic-pituitary-adrenal axis by inducing secretion of ACTH.
Ginseng increases the life span of cells in culture and stimulates nerve growth
factor. It has been shown to decrease platelet adhesiveness in animal models,
and may have a variable effect on the International Normalized Ratio (INR)
clotting time. Adverse reactions to ginseng are rare, but may include
nervousness and excitation, diarrhea, skin eruptions, and hypoglycemia.14
Rare endocrinologic effects include mastalgia and post-menopausal bleeding.
Ginseng can interact with antihypertensives, and Siberian ginseng has been shown
to interfere with digoxin levels.15 Goldenseal(Hydrastis canadensis) - Goldenseal was used by
the American Cherokee Indians who introduced it to the European settlers
primarily as a topical antiseptic and systemically for curing infections. It has
recently become popular again because of the widespread, but mistaken, belief
that it can mask illicit drugs in urine toxicology screens. It is currently used
as an antiseptic, and to treat digestive disorders (both diarrhea and
constipation), fluid overload, acne, sore throat, and to ward off infections
(especially when taken with echinacea and zinc). Its active substances are
alkaloids (hydrastine, berberine, canadine, and berber-astine). One of its main
bioactive components, berberine, is an effective antidiarrheal agent. One
controlled study showed it to reduce stool volumes and duration of diarrhea in
patients suffering from the effects of E. coli and V. cholera.16
Berberine is thought to act intraluminally and not systemically. It exerts
antimicrobial activity against several species of bacteria, fungi, and protozoa.
Additionally, it blocks adhesion of bacteria to epithelial cells, and protects
intestinal cells from the effects of toxins. Berberine also stimulates uterine
smooth muscle through an oxytocic effect and may induce abortions at high doses.
Another active component, hydrastine, has been reported to lower blood pressure
and stimulate peristalsis. It is also reported to be an antitussive (cough
suppressant). Because goldenseal has several active ingredients, undesirable
side effects may be present if it is taken in large doses. These side effects
may include mucosal irritation, GI tract upset, uterine contractions, neonatal
jaundice, hypertension, seizures, inotropic cardiac effects, and respiratory
failure. Large doses may also oppose the anticoagulant effects of heparin and
coumadin.17 Kava-kava (Piper methysticum) - This member of the pepper
family has been described as a natural sedative or "an herbal alternative to
Valium". It has become a popular anti-stress herb. In folklore it is known for
its anti-convulsive and sedative effects. Kava has played an important role in
many South Pacific societies. It is used in many of their most important
rituals. Recently, a man from the island of Tonga was arrested in San Mateo,
California, for driving while impaired after a six-hour kava ceremony at his
church. He appeared to be "driving under the influence" and was weaving between
lanes although he had not consumed any alcohol.18
Pyrones, the active agents in kava, seem to act as a muscle relaxant and produce
sedation. Additional effects may include loss of coordination, sluggish motor
reflexes, and, with heavy use, dilated pupils. Kavalactones (found in the root)
have been shown to relieve anxiety and pain, as well as to relax muscles in
laboratory animals. In humans, they have been shown to change brain activity (as
measured by EEG) without producing sedation.19
Reported side effects include muscle spasms, and an increase in episodes and
duration of impaired movements in a patient with Parkinson's disease. St. John's Wort (Hypericum perforatum) - This yellow
wildflower that grows wild throughout much of the world has been used for
thousands of years for a variety of conditions. It is named for St. John the
Baptist because it blooms around his feast day (June 24) and exudes a red color
symbolic of his blood. It is used commonly as an antidepressant, but is being
investigated for its anti-inflammatory, anti-infective, antiviral and
antineoplastic effects. Several studies and meta-analyses have concluded that it
is significantly more effective than placebo in treating mild to moderate
depression.20 It is prescribed as an
antidepressant by physicians in Germany up to four times more often than
Prozac®(fluoxetine).8 The mechanism of St.
John's wort's anti-depressant effects is only partially known. It was initially
thought to be via an MAOI-like action. Some in vitro studies demonstrated MAO
inhibition, but only at concentrations not found in vivo.21
The active ingredient is thought to be hypericin, which has a high affinity for
gamma-aminobutyric acid (GABA). The stimulation of GABA receptors is known to
have antidepressant effects. Other studies suggest that hypericin inhibits the
re-uptake of serotonin and may possibly inhibit the reuptake of norepinephrine
and dopamine as well. Altered receptor regulation is consistent with the several
week lag between drug ingestion and clinical effects.
Photosensitivity is a side effect associated with St. John's wort,
especially in fair-skinned individuals. It may exacerbate sunburn or sun
sensitivity if used with other photosensitizing drugs. Other reported reactions
include hypertension, headaches, nausea and vomiting, and stiff neck. Saw Palmetto(Serenoa repens) - Extracts from the fruit of
the saw palmetto have been used historically to treat urogenital problems. It is
a first-line treatment in much of Europe to improve the signs and symptoms of
benign prostatic hypertrophy.22 Saw palmetto
extract works by inhibiting the 5a-reductase enzyme,
which blocks the conversion of testosterone to dihydroxytestosterone, a major
growth stimulator of the prostate gland. The extract also blocks the prostatic
uptake of testosterone and dihydroxytestosterone without affecting serum
testosterone levels. Saw palmetto has an anti-inflammatory effect that is
thought to play a role in decreasing edema in the prostate.
Side effects from saw palmetto are rare, but may include gastrointestinal
tract upset, headache, and possible interactions with other hormonal therapies.
Valerian(Valeriana officinalis) - Valerian has been used
since the ninth century, A.D. as a calming and sleep-promoting agent. It acts as
a sedative, antispasmodic, and diuretic, and is used today to treat a myriad of
disorders including nervousness, anxiety, restlessness, headache, hysteria,
tension, headaches, fever, digestive problems, urinary tract disorders,
insomnia, depression, sleep disorders, pre-menstrual syndrome (PMS),
hyperactivity and hypochondria. Called the "Valium of the nineteenth century",
valerian is recognized world-wide for its relaxing effect on the body. German
health officials have approved it for use as a mild sedative and sleep aid,
based on several European clinical trials that demonstrate these effects. The
major constituents of the volatile oil found in the valerian root include bornyl
acetate, valerenic acid, and other sesquiterpenes. Some of these have been shown
to have a direct action on the amygdaloid body of the brain. Valerenic acid has
been shown to inhibit enzyme-induced breakdown of GABA in the brain, resulting
in sedation.23 Recent studies have shown that
the aqueous extract of the roots not only has effects on GABA(A) receptors, but
can also interact at other presynaptic components of GABAergic neurons.24
Valerian has a synergistic effect with alcohol, which may exaggerate the
side effects of each. A small percentage of consumers have experienced
paradoxical stimulation, consisting of restlessness and palpitations.25

Adverse Reactions

Dose-related Toxicity

There is known variation
between labeled and actual content of pharmacologically active components in
many different herbal products. Several consumer reports have shown vast
brand-to-brand variation. Variation in potency among different brands, as well
as batches within a brand, is most likely related to natural variation in crop
conditions and yield. The uncertainty as to how many species were used and how
the herbs were gathered, which plant parts were used, and how they were prepared
also lead to the unpredictability of the final product's active ingredient(s).
Herbal preparations that contain different plant subspecies, allergens, pollen,
molds, or other contaminants may have different pharmacological properties or
strengths. In addition, there are some herbs that are edible when immature, but
may be actually poisonous at maturity. Because of the lack of regulation in the
gathering and manufacturing of herbal products, many manufacturing companies may
not employ rigid quality control standards and do not evaluate their products
for purity and quality.

Plant Misidentification or
Adulteration

Many different types of
contaminants such as heavy metals, e.g., lead, arsenic, and mercury, as well as
pesticides, microbes, or microbial toxins have been found in various herbal
preparations. Certain Chinese herbs have been found to contain as many as 41
different types of drug adulterants in up 32% of pills.26
Indian traditional medicines sometimes contain bhasmas (metal oxides intended
for internal use), which are intentionally included in some products. In a
report of a 5-year study assessing the toxicological problems associated with
the use of traditional and herbal remedies in the United Kingdom, 12 cases of
poisoning by lead, arsenic, and mercury were identified.27
Acute aconitine poisoning has been reported in the Chinese literature and is a
known entity to practicing herbalists, although "Western" trained physicians may
be less aware of the possibility.28 Aconitine,
the poisonous alkaloid in the plant acotine, is cardiotoxic and can induce
life-threatening arrhythmias.

Herb-drug Interactions

Herb-drug interactions are
an important consideration, especially regarding pharmaceutical products with
narrow therapeutic indices. Several medicinal herbs and pharmaceutical drugs are
therapeutic at one dose but toxic at another. Interactions between the herbs and
the drugs may increase or decrease the pharmacological or toxicological effects
of either component. Synergistic therapeutic effects may complicate the dosing
of long-term medications. Because herbs are frequently marketed as multi-herb
products, the potential of drug and herb interactions are exponentially
increased in these products.

Specific Concerns

Several commonly used herbs
have the potential for causing troublesome reactions in patients, especially
those undergoing surgical procedures (Table 2).
Patients may manifest certain signs and symptoms intraoperatively due to
"unknown" causes unless it is realized that the patient is taking herbs.

Increased Bleeding Potential

Special care should be
taken in patients who are using several of the popular herbal products currently
available. Many of them, including feverfew, garlic, ginkgo, ginger, and ginseng
may alter platelet function, and increase bleeding potential, especially in
patients receiving concomitant anticoagulant or antithrombotic therapy. Modes of
action of the platelet dysfunction include inhibition of platelet aggregation,
decreased platelet adhesiveness, and inhibition of platelet activating factor.
Patients taking coumadin, heparin, aspirin, or nonsteroidal anti-inflammatory
drugs should be specifically educated as to possible side effects of increased
bleeding.

Potentiation of Anesthetic
Agents

Several herbal products act
on the central nervous system and may potentiate the effects of anesthetic
agents. Valerian, kava-kava, and St. John's wort may potentiate barbiturates and
benzodiazepines and may cause a prolongation of anesthetic effects.

Induction of the Cytochrome
P450 System - Decreased Drug Bioavailability

Extracts of St. John's wort
contain naphtodiantrons, which induce the CY P3A isoenzyme of the cytochrome
P450 complex. Additionally, the extract may induce intestinal P-glycoprotein
drug transporter, which may further contribute to a decreased oral
bioavailability of many drugs. Decreased plasma levels of drugs metabolized
through the P450 system may adversely affect patients. Examples of drugs that
may be affected include those used to treat heart disease (digoxin, diltiazem,
nifedipine, digitoxin, and beta adrenergic blockers), depression (imipramine,
amoxapine, and amitriptyline), seizures (carbamazepine, phenytoin, and
phenobarbital), certain cancers (cyclophosphamide, tamoxifen, taxol, and
etoposide) or to prevent transplant rejection (cyclosporine, rapamycin, or
tacrolimus) or pregnancy prevention (ethinyl estradiol).29
Specific examples include the decreased bioavailability of digoxin by 25-30%
after a 14-day administration of St. John's wort. Cases of decreased
cyclosporine bioavailability have been reported in cardiac transplant patients
taking St. John's wort, resulting in cellular transplant rejection.30
Similarly, plasma concentration of indinavir (a protease inhibitor used to treat
HIV), decreased by more than 50% in patients taking St. John's wort.31
A Food and Drug Administration public health advisory was issued (February 10,
2000) to warn health care professionals about the dangers associated with
decreased drug bioavailability associated with the concomitant administration of
St. John's wort.

Cardiovascular Instability

Ephedra has been implicated
in causing strokes, angina, arrhythmias, headaches, memory loss, panic attacks,
and death. Because of a number of reports of adverse events associated with the
ingestion of Ephedra, the Food and Drug Administration recently proposed limits
on dosage and duration of use,32 as well as
requested an independent review of those reports of adverse events related to
the use of Ephedra alkaloids to estimate the level of risk in using these herbal
products. That article by Haller and Benowitz, which appeared in The New England
Journal of Medicine in December of 2000, concluded that there might be a health
risk to some people with the use of Ephedra.33
The authors reviewed 140 reports of adverse events related to the use of dietary
supplements containing Ephedra alkaloids that were submitted to the FDA between
June 1, 1997 and March 31, 1999. They concluded that 31% of events were either
definitely or probably related to Ephedra use, and 31% were possibly related.33
Of those adverse events reported, almost half involved cardiovascular symptoms
and 18% involved the central nervous system. Hypertension was the single most
frequent adverse effect, followed by palpitation, tachycardia, stroke and
seizures. Ten events resulted in death and 13 events produced permanent
disability.33
Earlier in 2000, in the published minutes from the Public Meeting on the
Safety of Dietary Supplements Containing Ephedrine Alkaloids, American Herbal
Products Association (AHPA) President, Michael McGuffin, summarized an Ephedra
Survey undertaken by AHPA in early 2000. Their survey queried 42 manufactures
and/or marketers whose products had been listed in the FDA's initial Adverse
Event Report on June 4, 1997. Fourteen companies (33%) responded, and the
survey's conclusions were based on those responses. In summary, the AHPA Ephedra
Survey estimated total sales of products containing ephedrine alkaloids to have
been greater than 3 billion servings in 1999. They found that almost all of the
ephedrine products marketed by the Survey's respondents were in full conformity
with the industry established standards. Finally, the Survey recorded that
consumers of these products reported very few serious adverse events. AHPA's
conclusions from the compiled data were that "supplement products containing
ephedrine alkaloids are safe when responsibly manufactured, labeled and marketed
and responsibly used by consumers."
Ginseng has been implicated in causing tachycardia and/or hypertension,
especially when used concomitantly with other stimulants (such as caffeine). The
Ginseng Abuse Syndrome has been described as occurring in people who took
relatively large doses of the root (more than 3 gms/day). Symptoms included
diarrhea, skin eruption, nervousness, sleeplessness and hypertension.34

Toxicity

Hepatotoxicity is a
potentially fatal side effect of certain herbal medications. Although the
causality is difficult to prove, risks of toxicity are associated with the use
of certain herbal products.35
The use of echinacea can potentially cause hepatotoxicity with chronic use
and therefore should not be used with other known hepatotoxic drugs, such as
anabolic steroids, amiodarone, methotrexate, and ketoconazole. However,
echinacea lacks the 1,2 saturated necrine ring associated with hepatotoxicity of
pyrrolizidine alkaloids.36 Several cases of
acute hepatitis have been reported in patients taking herbal preparations
containing valerian for stress,37 but no
experimental data have been forthcoming to support the toxicity. A prospective
study from Sweden showed that liver enzyme abnormalities were more frequent in
patients who took herbal preparations, and that those abnormalities disappeared
in patients who discontinued taking the herbs.38
Patients with known liver dysfunction or receiving known hepatotoxic drugs
should be specifically warned about the use of herbals

Electrolyte Disturbance

Goldenseal root functions
as an aquaretic, not a diuretic. Diuretics enhance the excretion of both sodium
and water, while aquaretics only cause water excretion. Because it can cause
excretion of free water, but not sodium, goldenseal may actually worsen edema
and/or hypertension in patients taking this herb.

Conclusions

With the rapidly increasing usage of herbal products,
it is essential that the medical community recognize the fact that many patients
are taking potent "medicines" that were not prescribed by a physician, and that
these "medicines" may have serious consequences and side effects. Many questions
may be raised concerning the clinical implications of treating patients who are
taking various herbal remedies. The use of regional anesthetics, the appropriate
dose of heparin in patients undergoing cardiothoracic surgery, and the
adjustment of Dilantin doses are but a few of the questions that come to mind.
Until research has been done to address these and similar issues, there are no
specific guidelines to follow. To date, there is a paucity of anesthesia
literature addressing the use of herbs. An article in Anesthesiology appeared
recently describing which herbs were most commonly used and the patient profile
of those most likely to use herbal medications,39 but little else can be found
in "our" scientific literature. Both the American Society of Anesthesiologists
(ASA) and the New York State Society of Anesthesiologists (NYSSA) have addressed
some of the general problems associated with herbal medicines and anesthesia.
This information can be found on their web sites.40,41
ourselves (as well as our patients) about these alternative forms of
treatment, and to realize the implications that these herbal remedies may have
on our medical care of the patients. Extra care should be taken to obtain a
complete "herbal history" when seeing the patient preoperatively (Table
3). Patients should be taught the need to discuss
herbal usage with their health care providers, as well as the importance of
discontinuing those herbs prior to a surgical procedure (Table
4). Encouragement of open communication and greater
knowledge of alternative medical therapies by healthcare providers may help to
prevent adverse reactions or complications in today's surgical patients